Astrocyte glutamine synthetase: pivotal in health and disease
Abstract
The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate–glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.
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Glutamine synthetase (GS) catalyzes the condensation of ammonium and glutamate into glutamine.
“Complementarily, the cytoplasmic enzyme glutamine synthetase (GS) catalyzes the condensation of ammonium and glutamate into glutamine [24, 27, 29], which in turn can be reconverted into glutamate for use either as a neurotransmitter or energy substrate [21, 22, 23, 24, 25, 26, 27].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [24]
Astroglial cells are the main regulators of cerebral glutamate clearance and metabolism.
“The astroglial cells are the main regulators of cerebral glutamate clearance and metabolism [21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [24]
Glutamine can be reconverted into glutamate for use as a neurotransmitter or energy substrate.
“which in turn can be reconverted into glutamate for use either as a neurotransmitter or energy substrate [21, 22, 23, 24, 25, 26, 27].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [24]
GS can be upregulated by astrocytes and expressed by neurons in response to aging and AD.
“it has also been shown that GS can be upregulated by astrocytes [95] and expressed by neurons [24] in response to aging and AD.”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [24]
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“Astroglial cells are fundamental for brain development being, for example, chief promoters and supporters of synaptogenesis, synaptic maturation and maintenance ([13,14]).”
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Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
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- Authors
- Rose, C. F., Verkhratsky, A., & Parpura, V.
- Affiliations
- Centre Hospitalier de l’Université de Montréal (CA)
- University of Manchester (GB)
- University of Rijeka (HR)
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2013-11-20
- Volume
- 41
- Issue
- 6
- Pages
- 1518-1524
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W1832520743
- Cited by
- 224
- References
- 3
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 18 · 2023: 18 · 2022: 17 · 2021: 22 · 2020: 23 · 2019: 21 · 2018: 12 · 2017: 16 · 2016: 16 · 2015: 14 · 2014: 16
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Papyrus : Institutional Repository (Université de Montréal) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- astrocytes, glutamine synthetase, glutamate-glutamine cycle, glutamate homeostasis, ammonia detoxification, astrocyte function, neurotransmitter homeostasis, neurotoxicity
- MeSH terms
- Ammonia, Astrocytes, Disease, Glutamine, Glutamate-Ammonia Ligase, Health, Humans, Glutamic Acid
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